Cyclophanes and cages

Most of the known synthetic receptors, such as cryptands, cyclophanes, and cages, are homo-oligomeric structures, although more complex and unconventional topologies, such as interlocked and knotted molecules have recently proved their... 

The most important application of sulfone pyrolysis lies in the selective formation of cyclophanes and cage compounds (e.g. 18 and 19 in Scheme 6, [51,52]) from relatively conveniently available bisbenzyl sulfones. The preparative results of a sulfone pyrolysis strongly depend on the structure and the number of the sulfone groups present in the molecule and can vary between a few percent and almost quantitative yields [31b, 50-52]). 

Fig. 10. Schematic representation of guest-binding behavior of hybrid assemblies formed with peptide lipid 9 and cage-type cyclophanes 7 and 8, indicating conformational change of the host cavity...

Some of the chapters of this book are more focused on the synthetic developments in phosphorus containing materials. This is the case of Chap. 2, which reviews the aspects concerning phosphine acetylenic macrocycles and cages, and Chap. 12, which deals with the important field of P-based cryptands, cyclophanes, and corands. Chapter 4 addresses the potential applications of metal complexes containing anionic phosphoms chains for the synthesis of metal phosphides, whereas the synthesis of P-compounds via the metal catalysed addition of P-H bonds to unsaturated organic molecules is thoroughly reviewed in Chap. 8. 

In addition to macrocyclic hosts discussed above, many other molecules capable of selective complexation have been synthesized. They belong to so-called macrocyclic chemistry [30] encompassing crown ethers discussed in this Chapter, cryptands 61-63 [21], spherands 70 [31], cyclic polyamines 71 [32], calixarenes 18 [5], and other cyclophane cages such as 72 [33] to name but a few. Hemicarcerand 5 [2b] discussed in Chapter 1 and Section 7.3 also belongs to this domain. Typical macrocyclic host molecules are presented in Chapter 7. 

In order to construct a hydrophobic three-dimensional cavity that is in-tramolecularly limited in space, we have prepared cage-type cyclophanes by linking macrocyclic rings. First we prepared a macropolycyclic host, which is constructed with two rigid macrocyclic skeletons of different size, tetraaza[3.3.3.3]paracyclophane as the larger one and tetraazacyclotetradecane as the smaller one, and four flexible hydrocarbon chains that connect the two macrocycles [40]. The flexibility of four hydrocarbon chains connecting the two macrocycles allows the induced-fit host-guest interaction in aqueous media. 

The cage-type peptide cyclophanes (7 and 8) exhibit discrimination toward steroid hormones, as effected by hydrophobic and n-n interactions. In addition, the chirality-based discrimination between a- and -estradiol as well as between D- and L-amino acids bearing an aromatic moiety is performed on the basis of their capacity of forming efficient hydrogen bonding with the host molecules in aqueous media [41, 43]. 

Fig. 5A-C. Gel-filtration chromatograms on a column (column size, 10 mm (I.D.) x 200 mm flow rate, 2.0 cm min ) of Sephadex G-50 with aqueous phosphate buffer (10 mmol dm ) at pH 7.0 as eluent A cage-type cyclophane 8 alone (1.0 x 10" mol) B hybrid assembly formed with 7 (1.0 X 10" mol) and 9 (2.0 x 10" mol) C hybrid assembly formed with 8 (1.0 x 10" mol) and 9 (2.0 X 10" mol)...

The cage-type cyclophane furnishes a hydrophobic internal cavity for inclusion of guest molecules and exercises marked chiral discrimination in aqueous media. The host embedded in the bilayer membrane is capable of performing effective molecular recognition as an artificial cell-surface receptor to an extent comparable to that demonstarated by the host alone in aqueous media. 

The medium may have a marked effect on the shape of receptor molecules itself. Shape modifications could strongly influence their substrate binding properties, for instance in the case of amphiphilic cyclophane receptors subjected to hydrophobic-hydrophilic factors in aqueous solution. Such medium effects in action are visualized by the solid state structures of two different forms of the water-soluble hexasodium salt of the macrobicyclic cyclophane 66, which could be crystallized in two very different shapes an inflated cage structure 71 building up cylinders disposed in a hexagonal array and a flattened structure 72 stacked in molecular layers separated by aqueous layers in a lamellar arrangement [4.73]. These two... 

---